The effect of BMI on the outcomes of CDK 4/6 inhibitor therapy in HR-positive metastatic breast cancer patients.
Authors: Dilek Çağlayan, Mehmet Zahid Kocak, Caglayan Geredeli, Ali Murat Tatli, Melek Karakurt Eryılmaz, Sema Sezgin Göksu, Murat Araz, Mehmet Artac
Journal: Journal of Clinical Oncology (2022)

e13010 Background: The standard of care in patients with hormone receptor (HR) -positive metastatic breast cancer is a cyclin-dependent kinase (CDK) 4/6 inhibitor combined with endocrine therapy (ET). Preclinical studies show that metabolic processes and cell metabolism such as adipogenesis, lipid synthesis and glucose regulation is affected by cell cycle regulators such as CDK 4 and 6. There are limited data regarding the impact of body mass index (BMI) on the efficacy of cyclin-dependent kinase 4/6 inhibitors plus endocrine therapy (ET) in metastatic breast cancer. We aimed to investigate the effect of BMI on the progression-free survival (PFS) in HR-positive metastatic breast cancer who received CDK4/6 inhibitor. Methods: This study was conducted as a retrospective cohort study, and data were obtained from three institution medical records. Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitor (palbociclib or ribociclib) plus ET (letrozole, anastrozole, or fulvestrant) were enrolled in the study. 179 patients were enrolled in the study between the January 2018 and December 2021. The patients were divided into three groups according to BMI level as follows; group 1: 18.5-24.9 kg/m 2 , group 2: 25-29.9 kg/m 2 and group 3: ≥ 30 kg/m 2 . Median follow-up was 10.94 months. Categorical variables were compared using the chi-square test or two-sided Fisher’s exact test. Comparison of PFS and BMI categories were performed through Kaplan-Meier curve and log-rank test. Results: 179 patients were included the study (42 [24%] in group 1, 65 [36%] in group 2, and 72 [40%] in group 3). The 12-month PFS was 52.9% in group 1, was 72.2% in group 2 and was 56.5% in group 3. There was no significant different between the groups (p = 0.054). However, group 2 patients tend to have a better outcome in term of PFS. When palbociclib plus ET and ribociclib plus ET were evaluated separately, the 12-month PFS rates between the BMI groups were higher in group 2 patients who received palbociclib plus ET, but there was no statistical significance (Ribociclib plus ET: 63.2% in group 1, 73.3% in group 2, 59.7% in group 3, p = 0.51. Palbociclib plus ET: 44.3% in group 1, 71.5% in group 2, 52.8% in group 3, p = 0.07). Hematological and non-hematological toxicity were similar between BMI groups (p &gt; 0.05, for all). Adverse events of grade 3 or 4 occurred in 18 (42.9%) of 42 patients in group 1 and in 20 (30.8%) of 65 patients in group 2 and in 22 (30.6%) of 72 patients in group 3 (p = 0.34). Dose reduction for CDK4/6 inhibitors was also similar between groups (p = 0.42). Median PFS was not reached due to a limited number of events in each group. Conclusions: In this study, we demonstrated the tendency that overweight patients with metastatic breast cancer may benefit more from CDK4/6 inhibitors in term of PFS from interim analyses of our data. Similar toxicity rates and adverse events were observed in all BMI groups with CDK4/6 inhibitors plus ET.